be230cLecture5

j electrophysiology 2007 normal posijve adult

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Unformatted text preview: Jon Schneider and Mercola, Development, 2001 7 4/15/13 IGF2 Promotes ReplicaJon of Immature Cardiomyocytes Li et al. (Sucov), Development, 2011 McDevik and Laflamme, J. Mol. Cell Cardiol. 2005 Summary of Factors that Promote Cardiomyogenesis Notch hkp://www.youtube.com/watch?v=9NGcLngdd8s Stem Cell ­derived Cardiomyocytes are Physiologically Immature Calcium Transients visible by Fluo ­4 Small size and poorly organized myofibrils Punctate and uniform distribuJon of gap juncJons (rather than focused at intercalaJng disks) Slow upstroke Vmax (typically <20V/s as compared to adult ventricular cardiomyocytes with 100 ­150 V/s) Less well developed sarcoplasmic reJculum, making contracJlity more dependent on Ca entry rather than internal stores •  RelaJvely depolarized MDP and slow depolarizing current (phase 4) that contributes to automaJcity •  RelaJvely low acJon potenJal amplitude •  RelaJvely short acJon potenJal duraJon •  •  •  •  8 4/15/13 NegaJve Force ­Frequency RelaJonship in hESC ­cardiomyocytes Binah et al., J. Electrophysiology, 2007 Normal PosiJve Adult Cardiomyocyte Force ­Frequency RelaJonship (depends on controlling Ca2+ uptake) Effect of stimulation frequency on rates of force development and decay (dF/dt max and dF/dt min) was measured in six muscles from WT mice and in six muscles from phospholamban KO mice. Bluhm W F et al. Am J Physiol Heart Circ Physiol 2000;278:H249-H255 ©2000 by American Physiological Society What is Cardiac Commitment? During Embryo and ESC Cardiogenesis, the Cerberus ­1 Protein Inhibits Nodal/TGFβ and BMP and Drives Cardiomyocyte DifferenJaJon of Uncommiked MesP1+, Flk1+ Progenitors Endoderm Cerberus-1 BMP Nodal Uncommitted Kdr/ Flk1+, MesP1+ Multipotent Progenitors ?? TGFβ Nkx2.5+, Mef2c+ Committed Cardiac Precursors Cardiomyocytes Cai, W., et al. Circula>on Research 111, 876 ­881 (2012). Foley, A.C. et al. Developmental Biology 303, 57 ­65 (2007). Schneider, V.A. & Mercola, M. Curr Biol 9, 800 ­809 (1999). 9 4/15/13 Stepwise Recruitment of SWI/SNF to MyoD-target Genes by Pre-assembled Baf60c-MyoD Complex Forcales et al. The EMBO Journal 2011 Nucleosome OrganizaJon of ChromaJn ChromaJn Remodelling by SWI/SNF 10 4/15/13 AcetylaJon and MethylaJon ModificaJons Type of modification monomethylation dimethylation trimethylation Histone H3K4...
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